JPH10251350A - Antimicrobial polymer, its production and its use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject polymer that contains no active substance to be leached out by washing and has the antimicrobial action independent of pH by compolymerizing t-butylaminoethyl methacrylate and other aliphatic unsaturated monomers. SOLUTION: The objective copolymer is prepared by copolymerizing (A) t-butylaminoethyl methacrylate and (B) one or more kinds of other aliphatic unsaturated monomer, when necessary, (C) on a support. The component (B) is preferably a (meth)acrylate of the formula [R<1> is H, methyl; R<2> and R<3> are each H, a metallic atom, a branched or straight chain aliphatic, cyclic, heterocyclic or aromatic <=20C hydrocarbon (derived from carboxyl, carboxylate, sulfonate or an alkylamino). A plastic is preferably used as a material (C).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an antibacterial polymer obtained by copolymerizing t-butylaminoethyl methacrylate with one or more aliphatic unsaturated monomers, a method for producing the same and a use thereof.

Further, the present invention relates to an antibacterial polymer obtained by graft copolymerizing t-butylaminoethyl methacrylate and one or more aliphatic unsaturated monomers on a support, a method for producing the same, and a method for producing the same. About use.

[0003]

BACKGROUND OF THE INVENTION The colonization and propagation of bacteria on the surfaces of conduits, containers or packages is highly undesirable. Frequently, a mucus layer is formed that greatly increases the microbial population, negatively affecting water quality, beverage quality and food quality, and can also cause product spoilage and consumer health damage.

[0004] Bacteria must be kept away from all living areas where hygiene is important. This applies to textiles that come into direct contact with the body, especially textiles for the genital area and textiles for the sick and geriatric. In addition, bacteria
Furniture and equipment surfaces must be kept away from nursing wards, especially in the intensive care and infant care areas, hospitals, especially in medical operating rooms and isolation wards for dangerous infectious diseases, and in toilets.

[0005] Currently, equipment, furniture surfaces and textiles are used as a disinfectant to a greater or lesser extent, if necessary or as a precaution against bacteria or chemicals with a wide range of potent antimicrobial activity. Treated with the solvent as well as the mixture.
Such chemicals do not act specifically and frequently form degradation products that are themselves toxic, irritating or of health concern. It does not show suitability in the case of sensitive individuals who respond frequently.

Another treatment for bacterial growth on surfaces is to incorporate substances with antimicrobial activity into the matrix.

[0007] t-Butylaminoethyl methacrylate is a commercially available monomer of methacrylate chemistry and is used in copolymers especially as a hydrophilic component. EP-A-0 290 676 describes the use of various polyacrylates and polymethacrylates as matrices for immobilizing bactericidal quaternary ammonium compounds.

US Pat. No. 3,592,805
The specification discloses the systematic preparation of fungicides, in which a perhalogenated acetone derivative is reacted with a methacrylate ester, for example t-butylaminoethyl methacrylate.

US Pat. No. 4,515,910
The specification describes the use of polymers consisting of the hydrogen fluoride salt of aminomethacrylate in dental medicine. Hydrogen fluoride bound in the polymer slowly flows out of the polymer matrix and has an effect on caries.

From another industrial field, US patents (US Pat.
-PS) 4532269 discloses a terpolymer consisting of butyl methacrylate, tributyltin methacrylate and t-butylaminoethyl methacrylate. This polymer is used as an antimicrobial marine paint, where the hydrophilic t-butylaminoethyl methacrylate promotes slow erosion of the polymer and releases the highly toxic tributyltin methacrylate as an antimicrobial agent.

In these applications, the copolymers prepared with aminomethacrylate are merely a matrix or carrier material for the added germicidal active substance from which the active substance can diffuse or migrate. be able to. Such polymers can be used when the required minimum inhibitory concentration (MIK) at the surface is no longer achieved.
Despite varying degrees, it quickly loses its effect.

European Patent (EP-PS) No. 020312
In the specification, a method for producing acrylonitrile fiber having an antibacterial action is described. This antimicrobial effect results from the protonated amine as comonomer building block, with the use of the protonated species, inter alia, dimethylaminoethyl methacrylate and tert-butylaminoethyl methacrylate.

The antimicrobial action of the protonated surface, however, is significantly reduced by the loss of H ⁺ ions.

[0014]

Accordingly, the object underlying the present invention is to develop a material with antimicrobial properties which does not contain the active substance to be washed off and whose antimicrobial action is not pH-dependent. Was to do.

[0015]

SUMMARY OF THE INVENTION Surprisingly, by copolymerization of t-butylaminoethyl methacrylate with one or more other aliphatically unsaturated monomers on a support, or
It has been found that graft copolymerization of -butylaminoethyl methacrylate with one or more aliphatically unsaturated monomers results in a polymer having an antibacterial surface that is not impaired by solvent and physical stress and does not show migration. Was issued. In this case, it is not necessary to use other bactericidal agents.

Thus, the subject of the present invention is an antimicrobial polymer obtained by copolymerization of t-butylaminoethyl methacrylate with one or more other unsaturated aliphatic monomers.

Furthermore, the object of the present invention is that t-
An antibacterial polymer obtained by graft copolymerization of butylaminoethyl methacrylate with one or more other unsaturated aliphatic monomers.

[0018] Similarly, an object of the present invention is a process for the preparation of an antimicrobial polymer, characterized in that t-butylaminoethyl methacrylate and one or more aliphatically unsaturated monomers are graft-copolymerized on a support. is there.

Furthermore, the present invention is directed to a method for producing an antibacterial polymer, which comprises copolymerizing t-butylaminoethyl methacrylate with one or more aliphatic unsaturated monomers.

A further object of the present invention is the use of an antimicrobial polymer according to claims 1 and 2 for the manufacture of an article with an antimicrobial coating consisting of a polymer.

A further object of the invention is the use of an antimicrobial polymer according to claims 3 to 5 for the manufacture of an article with an antimicrobial coating consisting of a polymer.

The copolymerization of t-butylaminoethyl methacrylate with one or more other aliphatically unsaturated monomers can be carried out by graft copolymerization on a support, and the antibacterial action is further continued. It can also be maintained. For this purpose, all aliphatically unsaturated monomers, for example of the general formula:

[0023]

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Wherein R ¹ represents a hydrogen atom or a methyl group, and R ² represents a hydrogen atom, a metal atom or a branched or unbranched aliphatic, cycloaliphatic, heterocyclic or aromatic 20 A hydrocarbon group having up to carbon atoms, or a carboxyl group, a carboxylate group, a sulfonate group, an alkylamino group, an alkoxy group, a halogen, a hydroxy group, an amino group, a dialkylamino group, a phosphate group, a phosphonate group, a sulfate group, Up to 20 branched or unbranched aliphatic, cycloaliphatic, heterocyclic or aromatic carbon atoms derivatized by carboxamide, sulfonamido, phosphonamido or a combination of these groups And R ³ represents hydrogen or the same as R ² ].

Further, the general formula:

[0026]

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A vinyl compound of the general formula:

[0028]

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It is also possible to use the maleic acid and fumaric acid derivatives of the formula wherein R ⁴ represents a hydrogen atom, an aromatic group or a methyl group or the same as R ² ;
R ⁵ represents a hydrogen atom, a methyl group or a hydroxyl group, the same as R ² , or corresponds to an ether of composition OR ² .

As support materials, in general all plastics, with or without radiation-sensitive groups, such as polyurethanes, polyamides, polyesters, polyethers, polyether block amides, polystyrene, polyvinyl chloride, polycarbonate, organopoly Suitable are siloxanes, polyolefins, polysulfones, polyisoprenes, polychloroprenes, polytetrafluoroethylene (PTFE), corresponding copolymers and blends and natural or synthetic rubbers. The method according to the invention can also be applied to the surface of metal moldings, glass moldings or wood moldings which are painted or otherwise covered with plastic.

The surface of the support can be activated by a series of methods before the graft copolymerization. The support is advantageously preliminarily removed with a solvent in a known manner to remove oils, fats or other impurities.

Activation of the standard polymer can be effected by UV radiation. Suitable radiation sources are, for example, UV-excimer instruments (HERAEUS Noblelight, Hanau, Deutschland). Mercury lamps are also suitable for activating the substrate, as long as they emit significant radiation components in the said areas. The exposure time is generally between 0.1 seconds and 20 minutes, preferably between 1 second and 10 minutes.

Activation of a standard polymer using UV radiation
Further, it can be performed using an additional photosensitizer. For this, a photosensitizer, for example benzophenone, is applied to the surface of the support and irradiated. This is likewise effected using a mercury lamp with an exposure time of 0.1 seconds to 20 minutes, preferably 1 second to 10 minutes.

This activation is carried out in the case of the present invention in air,
High frequency plasma or microwave plasma in nitrogen or argon atmosphere (Hexagon, Fa. Technics Plasma, 85551)
Kirchheim, Deutschland). This exposure time is generally between 30 seconds and 30 minutes, preferably between 2 and 30 minutes.
10 minutes. Energy supply is 10 for laboratory equipment
0-500W, preferably 200-300W.

Further, a corona device (Fa. SOFTAL, Hambur)
g, Deutschland) can also be used for activation. The exposure time in this case is generally from 1 to 10 minutes, preferably from 1 to 10 minutes.
60 seconds.

Activation by electron or gamma radiation (eg from a cobalt 60 source) as well as by ozonation allows for short exposure times, which are generally between 0.1 and 60 seconds.

Flame treatment of the surface also causes this activation. Appropriate equipment, in particular equipment with a Barriere-Flammfront, can be easily assembled or, for example, Fa. ARCOTEC, 71297 M
Commercially available from Oensheim, Deutschland. This equipment can be operated with hydrocarbons or hydrogen as the combustion gas. In each case, an obstructive overheating of the support must be avoided, which is easily achieved by bringing the support surface opposite the flame-treated surface into intimate contact with the cooling metal surface. For this reason, activation by flame treatment is limited to relatively thin planar supports. Exposure time is generally 0.1
Seconds to 1 minute, preferably 0.5 to 2 seconds, in which case the distance between the support surface and the outer frame front is 0.2 to 5 cm, preferably 0.5 to 2 cm, not a bright flame. is there.

The support surface thus activated can be treated in a known manner, for example by dipping, spraying or brushing, with t-butylaminoethyl methacrylate and one or more other aliphatically unsaturated monomers, optionally in solution. Covered. Water and water-ethanol mixtures are preferred as solvents, but other solvents can also be used if they have sufficient solubility in the monomers and have good wetting of the material surface. Solutions having a monomer content of from 1 to 10% by weight, for example about 5% by weight, are practically advantageous, in general a coating with a layer thickness of more than 0.1 μm covering the support surface which adheres in a single application. Occurs.

The graft copolymerization of the monomers located on the active surface is preferably effected by radiation in the short-wave region of the visible region or by radiation in the long-wave region of the UV region of the electromagnetic radiation. For example, UV-excimer radiation with a wavelength of 250-500 nm, preferably 290-320 nm, is particularly suitable. Even in this case, a mercury lamp is suitable as long as it emits a significant radiation component in the above-mentioned region. The exposure time is generally between 10 seconds and 30 minutes, preferably between 2 and 15 minutes.

Copolymers using t-butylaminoethyl methacrylate as a comonomer constitutional unit exhibit intrinsic germicidal behavior even when not grafted to the support surface.

One possible embodiment of the present invention consists in carrying out the copolymerization of t-butylaminoethyl methacrylate with one or more other aliphatically unsaturated monomers on a support.

The polymer according to the invention, consisting of t-butylaminoethyl methacrylate and one or more other aliphatically unsaturated monomers, can be applied on the support in the form of a solution.

Suitable solvents are, for example, water, ethanol, methanol, methyl ethyl ketone, diethyl ether, dioxane, hexane, heptane, benzene, toluene, chloroform, dichloromethane, tetrahydrofuran and acetonitrile.

The solution of the polymer according to the invention is applied on a standard polymer, for example by dipping, spraying or painting.

If the polymers according to the invention are formed directly on the support surface without grafting, suitable initiators are added.

As an initiator, azonitrile, alkyl peroxide, hydrogen peroxide, acyl peroxide, peroxoketone, perester, peroxocarbonate,
Peroxodisulfates, persulfates and all customary photoinitiators, such as acetophenone and benzophenone, can be used.

The initiation of the polymerization can be effected thermally or by means of electromagnetic radiation, for example UV radiation or gamma radiation.

The products coated with the polymers according to the invention are:
It can be a medical or hygienic product. Similarly, the products obtained by the graft copolymerization according to the invention are:
It can be a medical or hygienic product.

The products coated with the polymers according to the invention are:
Medical products such as catheters, blood sacs, drainage,
It can be used for the manufacture of guidewires and surgical instruments.

Furthermore, the polymers according to the invention can be used for the production of hygienic products such as toothbrushes, toilet seats, combs and packaging materials.

[0051]

The following examples illustrate the invention: Example 1 19.2 g of tert-butylaminoethyl methacrylate, 2.6 g of methyl methacrylate and tetrahydrofuran 1
50 ml were heated to 60 ° C. under protective gas. After this temperature was reached, 0.33 g of azobisisobutyronitrile dissolved in 10 ml of tetrahydrofuran was added. 2
After 4 hours, the reaction was completed by incorporating the mixture into 1 l of a water / ice mixture. The reaction product was filtered off and washed with 300 ml of n-hexane, then the product was partitioned between several Soxhlets, extracted with water for 24 hours and then dried in vacuo at 50 ° C. for 12 hours.

Example 2 4 g of the copolymer from Example 1 were mixed with 40 m of tetrahydrofuran.
l. After dipping the polyamide 12-sheet in this solution for 5 seconds, removing it from the solution for 10 seconds, then dipping for another 5 seconds and subsequently drying at room temperature under normal pressure,
A uniform film of the copolymer was formed on the polyamide sheet. The sheet was then dried in a vacuum at 50 ° C. for 24 hours. Subsequently, the sheet is washed 5 times in water at 30 ° C. for 6 times.
Extracted for hours and then dried at 50 ° C. for 12 hours.

Example 3 4 g of the copolymer from Example 1 were mixed with 40 m of tetrahydrofuran.
l. The polyvinyl chloride sheet was immersed in the solution for 2 seconds, taken out of the solution for 10 seconds, then immersed for another 2 seconds, and subsequently dried at room temperature under normal pressure. Was. The sheet is then heated at 50 ° C. for 24 hours.
And dried in vacuum. Continue to put this sheet underwater for 5
Extraction was performed at 30 ° C. for 6 hours, and then dried at 50 ° C. for 12 hours.

Example 4 A polyamide 12-sheet was exposed to 172 nm radiation of an excimer radiation source (Fa. Heraeus) at a pressure of 1 mbar for 2 minutes. The sheet thus activated was placed in a radiation reactor under protective gas and fixed. Further, the sheet was treated in a protective gas stream with 3 g of t-butylaminoethyl methacrylate, 2 g of methyl methacrylate and 95 g of methanol.
20 ml of a mixture consisting of Close the irradiation room, 3
It was spaced 10 cm below an excimer irradiation unit (Fa. Heraeus) having a radiation of 08 nm wavelength. Irradiation was started and the irradiation time was 15 minutes. Subsequently, the sheet was taken out and rinsed with 30 ml of methanol. The sheet was then dried at 50 ° C. for 12 hours in vacuum.
The sheet was subsequently extracted five times in water at 30 ° C. for 6 hours and then dried at 50 ° C. for 12 hours.

Determination of the bactericidal action: The bactericidal action of the coated plastic was determined as follows: Klebsiel on a piece of sheet 2 × 2 cm in size.
la pneumoniae) was applied in an amount of 100 μl.
The bacteria were suspended in a PBS-suspension (phosphate-buffered-saline). The cell concentration was 10 ⁵ cells / ml of buffer. The droplet was incubated for up to 3 h. The piece of sheet was placed in a polystyrene petri dish wetted with 1 ml of water to prevent any drying. After the contact time, 100 μl of this was taken with an Eppendorf tip and diluted with 1.9 ml of PBS. 0.2 ml of this solution was plated on culture agar. The inactivation rate was calculated from the number of colonies that grew.

Test of coating stability: Before the determination of the bactericidal action, the coated sheets were subjected to the following pretreatments: A: washing in boiling water for 10 minutes B: 10 minutes in 96% ethanol solution Washing C: Washing in warm water at 25 ° C. for 10 minutes under ultrasonic treatment D: Without pretreatment Table 1 shows the measurement results in consideration of each pretreatment.

[0057]

[Table 1]

The antibacterial layer is grafted on the surface of the support,
Even after thermal, chemical or mechanical pretreatment, it also showed almost complete inactivation of the loaded bacteria. The physically adhered layer was not very stable to pretreatment by methods A, B and C.

In addition to the bactericidal action against Klebsiella pneumoniae described above, all the coated sheets were similarly Pseudomonas aeruginosa.
aeruginosa), Staphylococcus aureus (Stap
hylococcus aureus, Escherich
ia coli), Rhizopus oryzae,
Candida tropicalis and Tetrahymena pyriformi
s) showed antibacterial action. The inactivation rate after treatment D was in this case also higher than 99%.

Claims (16)

[Claims] 1. An antimicrobial polymer obtained by copolymerizing t-butylaminoethyl methacrylate with one or more other unsaturated aliphatic monomers. 2. The antimicrobial polymer according to claim 1, which is obtained by copolymerizing t-butylaminoethyl methacrylate with one or more other aliphatic unsaturated monomers on a support. 3. An antimicrobial polymer obtained by graft copolymerizing t-butylaminoethyl methacrylate with one or more other unsaturated aliphatic monomers on a support. 4. The antimicrobial polymer according to claim 3, which is obtained by activating the support before the graft copolymerization. 5. A photosensitizer obtained by activating the support with UV radiation, with or without additional photosensitizers, plasma treatment, corona treatment, flame treatment, ozone treatment, electrical discharge or gamma radiation. Item 7. The antibacterial polymer according to Item 4. 6. The method for producing an antibacterial polymer according to claim 1, wherein t-butylaminoethyl methacrylate is copolymerized with one or more aliphatic unsaturated monomers. 7. The method according to claim 6, wherein the copolymerization of t-butylaminoethyl methacrylate with one or more aliphatically unsaturated monomers is carried out on a support. 8. The preparation of the antimicrobial polymer according to claim 3, wherein t-butylaminoethyl methacrylate and one or more aliphatic unsaturated monomers are graft-copolymerized on a support. Method. 9. The method according to claim 8, wherein the support is activated before the graft copolymerization. 10. Activation of the support is provided by an additional photosensitizer,
10. The method of claim 9, wherein the method is performed with UV radiation, with or without plasma treatment, corona treatment, flame treatment, ozone treatment, electrical discharge or gamma radiation. 11. Use of an antimicrobial polymer according to claim 1 or 2 for producing an article with an antimicrobial coating comprising a polymer. 12. Use of the antimicrobial polymer according to claim 1 or 2 for producing a medical product with an antimicrobial coating comprising a polymer. 13. Use of an antimicrobial polymer according to claim 1 or 2 for producing a hygienic product with an antimicrobial coating consisting of a polymer. 14. Use of an antimicrobial polymer according to any one of claims 3 to 5 for producing an article with an antimicrobial coating comprising a polymer. 15. Use of an antimicrobial polymer according to any one of claims 3 to 5 for producing a medical product with an antimicrobial coating consisting of a polymer. 16. Use of an antimicrobial polymer according to any one of claims 3 to 5 for producing a hygienic product with an antimicrobial coating consisting of a polymer.